Effects of n-Octyl-β-D-Glucopyranoside on Human and Rat Erythrocyte Membrane Stability against Hemolysis

The practical importance for the pharmaceutical and cosmetics industries of the interactions between biological membranes and surfactant molecules has led to intensive research within this area. The interactions of non-ionic surfactant n-octyl-β-D-glucopyranoside (OG) with the human and rat erythrocyte membranes were studied. The in vitro hemolytic and antihemolytic activities were determined by employing a method in which both erythrocytes were added to the hypotonic medium containing OG at different concentrations, and the amount of haemoglobin released was determined. n-octyl-β-D-glucopyranoside was found to have a biphasic effect on both types of erythrocyte membrane. We also investigated the interactions of OG with the erythrocyte membrane in isotonic medium; the dose-dependent curves show similar behaviour in both human and rat erythrocytes. Our results showed that OG has greater antihemolytic potency on rat than on human erythrocytes; furthermore, rat erythrocytes were more sensitive than human erythrocytes to hypotonic shock. How the different lipoprotein structure of these erythrocytes determines a difference in antihemolytic activity is discussed

Choline modulation of the ABP1-40 channel reconstituited into a model lipid membrane

Nicotinic acetylcholine receptors (AChRs), implicated in memory and learning, in subjects affected by Alzheimer’s disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP) forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh) and in palmitoyl-oleoyl-phosphatidylcholine (POPC):Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min) and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD) spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs

AβP1-42 incorporation and channel formation in planar lipid membranes: the role of cholesterol and its oxidation products

Amyloid beta peptide (AP) is a natural peptide, normally released into the cerebrospinal fluid (CSF), that plays a key role in Alzheimer’s disease. The conversion of the peptide from a native soluble form to a non-native and often insoluble form, such as small and large aggregates, protofibrils and fibrils of AP appears to be implicated in the pathogenesis of AD. Although the molecular mechanisms of AP neurotoxicity are not fully understood, a large body of data suggests that the primary target of amyloid peptides is the cell membrane of neurons, that may modulate the structural and functional conversion of AP into assemblies involved in pathological processes. In our study, we provide a systematic investigation of AP1-42’s ability to incorporate and form channel-like events in membranes of different lipid composition and focus on cholesterol and its oxidation products. We propose that cholesterol and its oxidation products can be considered neuroprotective factors because a) by favouring AP1-42 insertion into membranes, the fibrillation/clearance balance shifts toward clearance; b) by shifting channel selectivity toward anions, the membrane potential is moved far from the threshold of membrane excitability, thus decreasing the influx of calcium into the cell

Heavy metals toxicity: effect of cadmium ions on Amyloid beta Protein 1-42. Possible implications for Alzheimer’s disease

Cadmium (Cd) is an environmental contaminant, highly toxic to humans. This biologically non-essential element accumulates in the body, especially in the kidney, liver, lung and brain and can induce several toxic effects, depending on the concentration and the exposure time. Cd has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows higher concentrations in brain tissues of AD patients than in healthy people, its implication in the formation of neurofibrillary tangles and in the aggregation process of amyloid beta peptides (AβPs). AβPs seem to have toxic properties, particularly in their aggregated state; insoluble AβP forms, such as small and large aggregates, protofibrils and fibrils, appear to be implicated in the pathogenesis of AD. In our study, we have evaluated the effect of Cd, at different concentrations, both on the AβP1-42 ion channel incorporated in a planar lipid membrane made up of phosphatidylcholine containing 30 % cholesterol and on the secondary structure of AβP1-42 in aqueous environment. Cadmium is able to interact with the AβP1-42 peptide by acting on the channel incorporated into the membrane as well as on the peptide in solution, both decreasing AβP1-42 channel frequency and in solution forming large and amorphous aggregates prone to precipitate. These experimental observations suggesting a toxic role for Cd strengthen the hypothesis that Cd may interact directly with AβPs and may be a risk factor in AD

Cholesterol modulates the interaction of some channel-forming peptides

The recent advances in membrane structure and function, describe the membrane as formed by microdomains enriched in cholesterol and glycosphingolipids or lipid rafts implicated in various dynamic cellular processes, such as protein sorting and trafficking, signal transduction processes, modulation of peptide incorporation and channel formation. Cholesterol is present in rapidly changeable pools tightly controlled by a feedback mechanism. The aim of this review is to provide some insight and commentary on how membrane cholesterol modulates the incorporation and channel formation of some peptides. The information gathered in many cases has been transferred to help design new therapeutic substances that improve membrane dysfunction or to biotechnological applications

Effect of cadmium ions on amyloid beta peptide 1-42 channel activity

Amyloid beta-peptide (Abeta) is a natural peptide of about 39-42 amino acids, which can aggregate and accumulate into senile plaques, one of the main pathological features in Alzheimer's disease (AD). There is extensive evidence that neurodegenerative pathologies, such as AD, are associated with protein misfolding and environmental factors, such as heavy metals, that are known to pollute the environment and can be taken up by the organism in food. They can accumulate within organs and tissues, with sometimes dramatic effects. There is increasing evidence that heavy metals can interact with amyloid beta peptides, contributing to the neurodegenerative events of AD. We investigated the effects of Cd++, an environmental contaminant on AbetaP1-42 aggregation, incorporation and channel formation into planar lipid membranes made up of phosphatidylcholine: cholesterol (70:30, w/w). Our results suggest that Cd++ interferes both with channels already incorporated into membranes and with peptides in solution. These findings provide important clues to the effect of this environmental contaminant on AbetaP1-42 that similarly to other metal ions, such as copper, zinc, aluminium and iron, can lead to abnormal interactions with proteins, contributing to cell damage